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Gene | PIK3CA |
Variant | E453K |
Impact List | missense |
Protein Effect | gain of function |
Gene Variant Descriptions | PIK3CA E453K lies within the C2 PI3K-type domain of the Pik3ca protein (UniProt.org). E453K results in increased phosphorylation of Akt and Mek1/2, enhanced cell survival, increased cell proliferation and migration, and is transforming in culture (PMID: 26627007, PMID: 29533785, PMID: 34779417). |
Associated Drug Resistance | |
Category Variants Paths |
PIK3CA mutant PIK3CA act mut PIK3CA E453K PIK3CA mutant PIK3CA exon8 PIK3CA E453K |
Transcript | NM_006218.4 |
gDNA | chr3:g.179210291G>A |
cDNA | c.1357G>A |
Protein | p.E453K |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_006218.3 | chr3:g.179210291G>A | c.1357G>A | p.E453K | RefSeq | GRCh38/hg38 |
XM_011512894 | chr3:g.179210291G>A | c.1357G>A | p.E453K | RefSeq | GRCh38/hg38 |
XM_011512894.2 | chr3:g.179210291G>A | c.1357G>A | p.E453K | RefSeq | GRCh38/hg38 |
NM_006218.4 | chr3:g.179210291G>A | c.1357G>A | p.E453K | RefSeq | GRCh38/hg38 |
XM_006713658.5 | chr3:g.179210291G>A | c.1357G>A | p.E453K | RefSeq | GRCh38/hg38 |
XM_006713658 | chr3:g.179210291G>A | c.1357G>A | p.E453K | RefSeq | GRCh38/hg38 |
XM_006713658.4 | chr3:g.179210291G>A | c.1357G>A | p.E453K | RefSeq | GRCh38/hg38 |
NM_006218 | chr3:g.179210291G>A | c.1357G>A | p.E453K | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
PIK3CA E453K PIK3CA E545A | stomach cancer | sensitive | Alpelisib | Preclinical - Cell culture | Actionable | In a preclinical study, Piqray (alpelisib) inhibited growth and induced cell cycle arrest and inhibited phosphorylation of Akt and S6 in a gastric cancer cell line harboring PIK3CA E545A and E453K in culture (PMID: 37493631). | 37493631 |
PIK3CA E453K PIK3CA E545A | stomach cancer | sensitive | Alpelisib + Dasatinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Sprycel (dasatinib) to Piqray (alpelisib) treatment resulted in an increased inhibition of proliferation in a gastric cancer cell line harboring PIK3CA E545A and E453K in culture (PMID: 37493631). | 37493631 |
PIK3CA E453K PIK3CA E545A | stomach cancer | sensitive | A-1331852 + Alpelisib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Piqray (alpelisib) and A-1331852 synergistically inhibited viability in a gastric cancer cell line harboring PIK3CA E545A and E453K in culture (PMID: 37493631). | 37493631 |
FGFR2 T319I PIK3CA N345K PIK3CA E453K | Her2-receptor negative breast cancer | predicted - resistant | Inavolisib | Case Reports/Case Series | Actionable | In a clinical case study, FGFR2 T319I was identified in circulating tumor DNA at the time of progression on Inavolisib (GDC-0077) in a patient with ESR1-positive, ERBB2 (HER2)-negative breast cancer harboring PIK3CA N345K and E453K (PMID: 37916958). | 37916958 |
PIK3CA E453K PIK3CA H1047R | estrogen-receptor positive breast cancer | predicted - sensitive | RLY-2608 | Case Reports/Case Series | Actionable | In a clinical case study, treatment with RLY-2608 resulted in a partial response with a reduction in liver, lung, and soft tissue target lesions in a patient with ESR1/PGR-positive, ERBB2 (HER2)-low breast cancer harboring PIK3CA H1047R and PIK3CA E453K (PMID: 37916956; NCT05216432). | 37916956 |